This proposal requests funds for a Siemens Eclipse HP Cyclotron in support of a highly successful positron emission tomography (PET) imaging research program that has been operational at the University of Pittsburgh since 1992. This vibrant research program is presently supported by 28 NIH-funded grants as well as several foundation and industry supported research projects from a group of 25 investigators from 8 academic departments of the University Of Pittsburgh School Of Medicine. This group has an impressive record of publication and achieving translational research successes such as the development of the PET/CT scanner and the amyloid imaging agent [11C]Pittsburgh-compound B (PiB) that is now being used worldwide in Alzheimer's disease research and clinical trials. The Eclipse HP will replace a legacy Siemens RDS-112 cyclotron, installed in 1992, which has been declared end-of-life by the manufacturer and retains only limited serviceability. The cyclotron is a key piece of equipment for any PET research program as the radionuclides used in a majority of the included project summaries have short half-lives that necessitate on-site production. Failure of the RDS-112 would represent a significant and detrimental interruption to ongoing NIH-sponsored research. In addition to providing a critical upgrade to existing infrastructure, several features of the Eclipse HP system will significantly enhance the PET research program. The deep-valley design of the Eclipse HP electromagnets provides improved beam transmission, reduced levels of internal activation, and higher production yields, while the single-coil magnet design drastically reduces power consumption. A second advantage of the proposed Eclipse HP configuration is the use of dual 4-position target carousels for a total of eight targets. The current RDS-112 system has four fixed beam lines, each with only one stationary target- thus limiting target utilization. The increased number of targets in the proposed Eclipse HP configuration as well as flexibility in dual target irradiation will represent a dramatic improvement in our radionuclide production capacity. The requested accessories, which include a remote automated gas-phase system for the production of [11C]MeI and incorporation platforms for both carbon-11 and fluorine-18, will allow us to realize the maximum efficiencies of the new cyclotron by enabling quick turnaround times for serial radiopharmaceutical productions. Realizing these efficiencies is of paramount importance as the RDS-112 presently supplies radiopharmaceuticals for two human Siemens HR+ PET scanners and two preclinical microPET scanners. The 19 major and 3 minor user projects described in this proposal will benefit from the sitting of a modern and currently supported cyclotron that will maintain the radiopharmaceutical production capabilities of the PET Facility for the foreseeable future. In addition, the increased radionuclide production capacity of the Eclipse HP will allow existing PET scanners to be more completely utilized, resulting in a greater output of studies, and will support continued expansion of the scope of PET imaging research conducted at the institution. PUBLIC HEALTH RELEVANCE: The Siemens Eclipse HP cyclotron requested will produce short-lived radioactive materials in support of a highly successful positron emission tomography (PET) imaging research program at the University of Pittsburgh, which is presently supported by 28 NIH funded grants that use PET imaging in novel biomedical investigations across a spectrum of diseases. The requested cyclotron and accessories will replace a legacy cyclotron installed in 1992 that is no longer supported by the vendor and facilitate a much needed increase in the PET Facility's production capacity. If awarded, this proposal is expected to have a significant impact on American jobs both at the institution (4-5 new jobs created, 40+ jobs maintained) and at the vendor (75+ jobs maintained at Siemens and its suppliers), while realizing an energy savings in terms of electricity use that is equivalent to the usage of 13 average American households.